Virtual screening and structure optimization of xanthine oxidase inhibitory peptides from whole protein sequences of Pacific white shrimp via molecular docking.

Xanthine oxidase (XO) inhibitory peptides are safer than conventional pharmacological therapy in relieving hyperuricemia. However, traditional enzymatic hydrolysis, separation, and purification techniques for bio-active peptide preparation are time-consuming, inefficient, and labor-intensive. In this study, molecular docking and BLAST were used to virtually screen XO inhibitory peptides from whole protein sequences of Pacific white shrimp according to the bio-active peptides database, and the structure of peptides was optimized based on the structure-effective relationship. Seven new XO inhibitory peptides were virtual screened rapidly from Pacific white shrimp, and YNITGW (IC50 = 9.78 ± 0.13 mM) showed the strongest activity. The results of YNITGW optimization showed that the insertion of Trp residue in the middle position of peptides could effectively enhance the activity. This study revealed that screening and optimizing peptides by molecular docking were a novel and feasible method to obtain bio-active peptides.

Identification and Anti-Hyperuricemic Activity of Xanthine Oxidase Inhibitory Peptides from Pacific White Shrimp and Swimming Crab Based on Molecular Docking Screening.

The xanthine oxidase (XO) inhibitory peptides from pacific white shrimp or swimming crab were identified by molecular docking, and the anti-hyperuricemic activity of the peptides was confirmed in hyperuricemic cells. In our study, 17 novel XO inhibitory peptides were purified from pacific white shrimp or swimming crab, and Ala-Glu-Ala-Gln-Met-Trp-Arg (AEAQMWR, 891.01 Da, IC50 = 8.85 ± 0.05 mM) exhibited the greatest XO inhibitory activity in vitro. Molecular docking results indicated that attractive charge, salt bridge, and hydrogen bond showed a crucial effect on the interactions of XO inhibitory peptides with the pivotal residues of Arg880, Glu802, and Glu1261. In addition, XO inhibitory peptides alleviated hyperuricemia by inhibiting inflammation and preventing increased uric acid transporter expression levels in hyperuricemia cells. Overall, these results further confirmed that screening of XO inhibitory peptides rapidly via molecular docking was feasible.

Exploration, sequence optimization and mechanism analysis of novel xanthine oxidase inhibitory peptide from Ostrea rivularis Gould.

Xanthine oxidase (XO) inhibitory peptides are secure and efficient functional food ingredients for treating or alleviating hyperuricemia (HUA). In this study, ultrafiltration and molecular exclusion chromatography were used to separate and purify enzymatic lysate of oyster protein, three novel peptides (ALSGSW, GGYGIF and MAIGLW) with strong XO inhibitory activity were screened by LC-MS/MS identification and molecular docking technology. Then, the mechanism of action between peptides and the XO was revealed by molecular docking technology, and the structure of the peptide was rationally designed on this basis. The results showed that replacing N-terminal Gly of peptide GGYGIF with Trp can significantly improve its XO inhibition rate, and peptides formed by the simple structure amino acid was connected to the aromatic amino acids has preferable inhibitory activity. These results showed that oyster was a good source of XO peptide inhibitors, molecular docking technology was an effective tool for obtaining highly active peptides.

Glycated fish protein supplementation modulated gut microbiota composition and reduced inflammation but increased accumulation of advanced glycation end products in high-fat diet fed rats.

This study first investigates how the intake level of glycated fish protein (GP), enriched with Amadori products, affects gut health by modifying the fermentation of gut microbiota and accumulation of advanced glycation end products (AGEs) in rats fed a high-fat diet. Hyperlipidemic rats were fed a fish protein (FP) control diet, 6% low-level GP (L-GP) diet, and 12% high-level GP (H-GP) diet for four weeks. Compared to the FP diet, the GP diet greatly changed the pattern of protein fermentation and reduced inflammation markers and blood lipids, but increased the AGE plasma accumulation and fecal excretion. Furthermore, the GP supplementation significantly decreased Ruminiclostridium_6 and Desulfovibrio (p < 0.05), and the L-GP diet showed more effects on the increase of butyrate-producing Ruminococcus_1 and Roseburia, while the H-GP diet considerably decreased Helicobacter and Lachnospiraceae_NK4A136_group. Correlation-type principal-component analysis (PCA) clearly indicated that these biological effects of intake of GP were related to the modulation of gut microbiota composition and fermentation metabolite profiles. Overall, the low intake level of glycated fish protein may have a more beneficial effect on gut health.

Modifications in gut microbiota and fermentation metabolites in the hindgut of rats after the consumption of galactooligosaccharide glycated with a fish peptide.

The aim of this research was to investigate the impact of a diet containing galactooligosaccharide (GOS)-fish peptide (FP) conjugates prepared via Maillard reaction on the colonic fermentation properties and the composition of gut microbiota in Sprague-Dawley rats. The rats were fed the GOS diet, FP diet, GOS and FP mixture (GOS/FP) diet, GOS glycated with FP (80 °C for 120 min, G-GOS/FP) diet, or control (CK) diet for three weeks. Compared to the GOS/FP diet, the G-GOS/FP diet greatly changed the pattern of SCFA production in the hindgut of rats, by increasing the total SCFA (44%), butyrate (55%) and propionate (1.23-fold) levels in the proximal colon, and the butyrate levels (74%) in the distal colon, and decreased the production of ammonia in feces (P < 0.05). The G-GOS/FP altered the colonic microbiota by increasing (P < 0.05) the relative abundance of Anaerovibrio (7.43-fold) and Prevotella-9 (2.47-fold), and by decreasing (P < 0.05) the relative abundance of Alloprevotella (0.57-fold) and Holdemanella (0.64-fold), and showed a similar relative abundance of Bifidobacterium, when compared with GOS/FP. The GOS/FP diet increased the number of Lactobacillus and the intensity of fermentation in the cecum, but the G-GOS/FP diet and GOS diet did not have these effects, showing that the glycation clearly altered the fermentability of the fish peptide. It is concluded that the glycation-induced modification of GOS by mild thermal treatments showed its fermentation persistence in the colon of the host, and improved some prebiotic activities of GOS. These results may provide new strategies for oligosaccharides in combination with peptides to modulate the intestinal environment to promote human health.